In vitro functional alterations in the hematopoietic system of adult patients with acute lymphoblastic leukemia

In previous studies, we have demonstrated that progenitor cell-enriched marrow cell populations from patients with myeloid leukemia - including both acute (AML) and chronic (CML) - show severe functional alterations when cultured in stroma-free liquid cultures supplemented with stimulatory cytokines. In trying to expand our characterization of the biology of leukemic cells, in the present study we have used a similar approach and analyzed the in vitro growth of equivalent cell populations from patients with acute lymphoblastic leukemia (ALL). ALL marrow cell populations -enriched for hematopoietic progenitors by means of a negative selection procedure- were assessed for their proliferation and expansion potentials, in liquid cultures supplemented with a mixture of early- and late-acting recombinant stimulatory cytokines, throughout a 25-day culture period. ALL cells, although capable of responding to the stimulatory signals provided by hematopoietic stimulators, showed deficient proliferation potentials (reduced capacity to generate more nucleated cells), as compared with their normal counterparts. The capacity to generate myeloid and erythroid progenitors was also significantly reduced in ALL cultures. Interestingly, the functional alterations observed in ALL cultures (i.e., deficient proliferation and expansion potentials) were more pronounced in those from Ph+ patients than in those from Ph- patients. This study indicates that bone marrow cell populations - enriched for hematopoietic progenitor cells - from ALL patients possess deficient proliferation and expansion potentials in vitro, and that such functional alterations are more severe when cells are derived from Ph+ patients, as compared to their Ph- counterparts.     

New perspectives in B-1 B cell development and function

In contrast to the predominant population of B-2 B cells produced in the bone marrow, B-1 B cells are a minor population of B lymphocytes that are found in multiple tissues, including the pleural and peritoneal cavities in mice. Although the role of B-1 B cells as effectors of innate-like immunity is widely accepted, their developmental origin has been controversial. This review highlights recent experimental data from murine studies supporting the hypothesis that B-1 B cells belong to a developmental lineage distinct from B-2 B cells, and draws attention to recent studies that have defined new roles for the B-1a and B-1b B-cell subsets in the response to bacteria and self-antigens.     

Lymphatic absorption of α-linolenic acid in rats fed flaxseed oil-based emulsion

The bioavailability of α-linolenic acid (ALA) from flaxseed oil in an emulsified form v. a non-emulsified form was investigated by using two complementary approaches: the first one dealt with the characterisation of the flaxseed oil emulsion in in vitro gastrointestinal-like conditions; the second one compared the intestinal absorption of ALA in rats fed the two forms of the oil. The in vitro study on emulsified flaxseed oil showed that decreasing the pH from 7·3 to 1·5 at the physiological temperature (37°C) induced instantaneous oil globule coalescence. Some phase separation was observed under acidic conditions that vanished after further neutralisation. The lecithin used to stabilise the emulsions inhibited TAG hydrolysis by pancreatic lipase. In contrast, lipid solubilisation by bile salts (after lipase and phospholipase hydrolysis) was favoured by preliminary oil emulsification. The in vivo absorption of ALA in thoracic lymph duct-cannulated rats fed flaxseed oil, emulsified or non-emulsified, was quantified. Oil emulsification significantly favoured the rate and extent of ALA recovery as measured by the maximum ALA concentration in the lymph (Cmax?=?14?mg/ml at 3?h in the emulsion group v. 9?mg/ml at 5?h in the oil group; P?相似文献   

Adenosine A(2A) receptor activation promotes wound neovascularization by stimulating angiogenesis and vasculogenesis

Recent reports indicate that circulating endothelial progenitor cells (EPCs) may be recruited to sites of neovascularization where they differentiate into endothelial cells (EC). As we have previously demonstrated that adenosine A(2A) agonists promote neovascularization in wounds, we sought to determine whether adenosine A(2A) receptor agonist-augmented wound healing involves vessel sprouting (angiogenesis) or EPC recruitment (vasculogenesis) or both. Four weeks after bone marrow reconstitution from donor FVB/N Tie2GFP transgenic mice, two full-thickness excisional wounds were performed on the dorsum of FVB/N wild-type mice and treated with either an A(2A) receptor agonist (CGS-21680) or vehicle alone. Vessel density, as measured by CD31 staining, and density of EPC-derived vessels, as measured by GFP expression, were quantified in a blinded fashion using two-color fluorescence microscopy. We observed nearly a threefold increase in CD31-positive vessels and a more than 10-fold increase in GFP-positive cells in A(2A) agonist-treated 3-day old wounds, but by 6 days after wounding the differences between A(2A) agonist-treated and vehicle-treated wounds were no longer statistically significant. In conclusion, this is the first evidence that an exogenous agent such as an adenosine A(2A) receptor agonist increases neovascularization in the early stages of wound repair by increasing both EPC recruitment (vasculogenesis) and local vessel sprouting (angiogenesis).     

Epidemiologic genotyping of methicillin-resistant Staphylococcus aureus by pulsed-field gel electrophoresis at a university hospital and comparison with antibiotyping and protein A and coagulase gene polymorphisms

A total of 124 methicillin-resistant Staphylococcus aureus (MRSA) isolates were ascertained at the University Hospital of the Canary Islands between January 1997 and April 2000. Genotyping included pulsed-field gel electrophoresis (PFGE) (SmaI digestion) and PCR-restriction fragment length polymorphism (PCR-RFLP) analysis for the coagulase (coa) and protein A (spa) genes. Antibiotic resistance was the main phenotypic marker correlated with genotyping results. Three main PFGE types were detected: A (with 12 subtypes), B (with 2 subtypes), and C. PFGE type A1 was the most commonly found (61% of isolates) and the one responsible for all the epidemic outbreaks. Other genetics markers used (coa and spa RFLPs) were significantly correlated with the PFGE types detected (P < 0.001). These PCR-RFLP assays were useful as molecular markers for a quick, preliminary study of MRSA outbreaks.